The first component of the development award will be formal training in biochemistry, cellular biology, and physiology. This formal training will be augmented by professional interactions with clinical physicians and a mentored research effort in the development of near-infrared sensors for the monitoring of hemodialysis dose. The initial research component of this work will be the development of an all-optical sensor for the on-line measurement urea concentration in spent dialysate. An effective on-line urea sensor will allow regular, sample-free monitoring and optimization of hemodialysis dose. The sensor will also be adapted for measurements in the extracorporeal whole blood stream between the patient and the dialyzer. The measurement of urea in whole blood will provide a measurement of dose that is more directly related to current blood-based dose quantitation. Because near-infrared sensing technology permits simultaneous quantification of multiple analytes, the sensor will also be applied to quantification of other blood components, including serum albumin, serum creatinine, hematocrit, and uremic toxins, including hippuric acid and indoxyl sulfate. The capacity to monitor these additional analytes every dialysis session will be of substantial benefit to clinical physicians working with patients suffering from either end-stage or acute renal failure. Finally, the near- infrared sensor will be applied to non-invasive, in vivo measurements of urea in peripheral tissue sites. The information provided by such a measurement will be invaluable for the study of urea disequilibrium during dialysis and as a potentially rebound-free quantification of delivered dose. Initial instrument development will be performed in a laboratory environment using an in vitro model for sensor optimization. Calibration models will be generated for urea and other analytes. Sensor operation will then be validated in the clinical setting.